As the largest individual contributor of freshwater inflow to the basin, the Rhone River is likely to be one of the main sources of microplastics (MPs) to the Mediterranean Sea. In order to predict the fate of MPs discharged by the Rhone River, an innovative 3D Lagrangian dispersion of its particles associated with vertical velocities was modeled in Mediterranean ocean currents. Through winter and summer scenarios, the seasonal variability of transfers and the corresponding accumulation areas were depicted in the Northwestern Basin according to hydrodynamic conditions on the continental shelf of the Gulf of Lion and to the frontal dynamics from the Pyrenees to the North Balearic fronts. Our results indicated that MP transfers were driven by mesoscale and sub-mesoscale structures, resulting in steep concentration gradients across fronts during summer, while winter energetic mixing favored a more efficient and homogeneous spreading. After a year of drift, high MP retention (up to 50%) occurred in the coastal zone of the Gulf of Lion near the river mouth, with a large contribution of sinking MPs and an increase in stranding during the highest freshwater inflows of the winter season. Conversely, up to 60% of the floating MPs were exported to the Algerian Basin and then to the Eastern Mediterranean. This west-to-east transfer led to significant stranding on the islands, prevailing on the northern coasts of the Balearic Islands in winter (6% of floating inputs) and on the western coasts of Corsica and Sardinia in summer (13%). The southern Mediterranean coasts, from Algeria to Tunisia, represented also a major sink for floating debris with stranding ranging from 9 to 35% of MPs discharged in winter and in summer, respectively. We estimated that 3.5 to 5 t of the Rhone MPs remained in the surface layer at the end of the year, with high concentrations in the Ionian Sea..